Nature aging最新文献_第10页

Using RNA therapeutics to promote healthy aging 利用RNA疗法促进健康衰老。

IF 19.4

Nature aging Pub Date : 2025-06-11 DOI: 10.1038/s43587-025-00895-1

Shuying Chen, Qian Chen, Xinru You, Zhuoming Zhou, Na Kong, Fabrisia Ambrosio, Yihai Cao, Reza Abdi, Wei Tao

{"title":"Using RNA therapeutics to promote healthy aging","authors":"Shuying Chen, Qian Chen, Xinru You, Zhuoming Zhou, Na Kong, Fabrisia Ambrosio, Yihai Cao, Reza Abdi, Wei Tao","doi":"10.1038/s43587-025-00895-1","DOIUrl":"10.1038/s43587-025-00895-1","url":null,"abstract":"Aging is characterized by a gradual decline of cellular and physiological functions over time and an increased risk of different diseases. RNA therapeutics constitute an emerging approach to target the molecular mechanisms of aging and age-related diseases via rational design and have several advantages over traditional drug therapies, including high specificity, low toxicity and the potential for rapid development and production. Here, we discuss the latest developments in RNA therapeutics designed to promote healthy aging, including RNA activation, messenger RNA therapy, RNA interference, antisense oligonucleotides, aptamers and CRISPR–Cas-mediated RNA editing. We also review the latest preclinical and clinical studies of RNA technology for treating age-related diseases, including neurodegenerative, cardiovascular and musculoskeletal diseases. Finally, we discuss the challenges of RNA technology aimed at supporting healthy aging. We anticipate that the fusion of RNA therapeutics and aging biology will have an important effect on the development of new medicines and maximization of their efficacy. Chen and colleagues explore how RNA therapeutics targeting mechanisms of aging can be used to treat age-related diseases and promote healthy aging. They discuss current preclinical and clinical progress, along with key challenges and future directions.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 6","pages":"968-983"},"PeriodicalIF":19.4,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 19.4

Nature aging Pub Date : 2025-06-10 DOI: 10.1038/s43587-025-00891-5

引用次数: 0

Recurrent somatic mutation and progerin expression in early vascular aging of chronic kidney disease 慢性肾脏疾病早期血管老化的复发性体细胞突变和progerin表达。

IF 19.4

Nature aging Pub Date : 2025-06-10 DOI: 10.1038/s43587-025-00882-6

Gwladys Revêchon, Anna Witasp, Nikenza Viceconte, Hafdis T. Helgadottir, Piotr Machtel, Fabiana Stefani, Daniel Whisenant, Agustin Sola-Carvajal, Dagmara McGuinness, Nadia O. Abutaleb, Gonzalo Artiach, Emelie Wallén Arzt, Inga Soveri, Anne Babler, Susanne Ziegler, Rafael Kramann, Magnus Bäck, Anders Thorell, George A. Truskey, Lars Wennberg, Paul G. Shiels, Annika Wernerson, Peter Stenvinkel, Maria Eriksson

{"title":"Recurrent somatic mutation and progerin expression in early vascular aging of chronic kidney disease","authors":"Gwladys Revêchon, Anna Witasp, Nikenza Viceconte, Hafdis T. Helgadottir, Piotr Machtel, Fabiana Stefani, Daniel Whisenant, Agustin Sola-Carvajal, Dagmara McGuinness, Nadia O. Abutaleb, Gonzalo Artiach, Emelie Wallén Arzt, Inga Soveri, Anne Babler, Susanne Ziegler, Rafael Kramann, Magnus Bäck, Anders Thorell, George A. Truskey, Lars Wennberg, Paul G. Shiels, Annika Wernerson, Peter Stenvinkel, Maria Eriksson","doi":"10.1038/s43587-025-00882-6","DOIUrl":"10.1038/s43587-025-00882-6","url":null,"abstract":"Early vascular aging plays a central role in chronic kidney disease (CKD), but its molecular causes remain unclear. Somatic mutations accumulate in various cells with age, yet their functional contribution to aging tissues is not well understood. Here we found progerin, the protein responsible for the premature aging disease Hutchinson–Gilford progeria syndrome, steadily recurring in vascular smooth muscle cells of patients with CKD. Notably, the most common progeria-causing mutation, LMNA c.1824C>T, was identified as a somatic mutation in CKD arteries. Clusters of proliferative progerin-expressing cells in CKD arteries and in vivo lineage-tracing in mice revealed clonal expansion capacity of mutant cells. Mosaic progerin expression contributed to genomic damage, endoplasmic reticulum stress and senescence in CKD arteries and resulted in vascular aging phenotypes in vivo. These findings suggest that certain somatic mutations may be clonally expanded in the arterial wall, contributing to the disease-related functional decline of the tissue. Progerin, a truncated version of lamin A, causes Hutchinson–Gilford progeria syndrome characterized by premature aging and cardiovascular complications. Here the authors show that the most common progeria-causing mutation, LMNA c.1824C>T, is a somatic mutation in arteries from patients with chronic kidney disease, and that clonal propagation of the mutation in the vascular wall results in vascular aging phenotypes in mice.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 6","pages":"1046-1062"},"PeriodicalIF":19.4,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Boosting angiotensin-converting enzyme (ACE) in microglia protects against Alzheimer’s disease in 5xFAD mice 提高小胶质细胞中的血管紧张素转换酶（ACE）可预防5xFAD小鼠的阿尔茨海默病。

IF 19.4

Nature aging Pub Date : 2025-06-09 DOI: 10.1038/s43587-025-00879-1

Andrew R. Gomez, Hyae Ran Byun, Shaogen Wu, A. K. M. Ghulam Muhammad, Jasmine Ikbariyeh, Jaelin Chen, Alek Muro, Lin Li, Kenneth E. Bernstein, Richard Ainsworth, Warren G. Tourtellotte

{"title":"Boosting angiotensin-converting enzyme (ACE) in microglia protects against Alzheimer’s disease in 5xFAD mice","authors":"Andrew R. Gomez, Hyae Ran Byun, Shaogen Wu, A. K. M. Ghulam Muhammad, Jasmine Ikbariyeh, Jaelin Chen, Alek Muro, Lin Li, Kenneth E. Bernstein, Richard Ainsworth, Warren G. Tourtellotte","doi":"10.1038/s43587-025-00879-1","DOIUrl":"10.1038/s43587-025-00879-1","url":null,"abstract":"Genome-wide association studies have identified many gene polymorphisms associated with an increased risk of developing late-onset Alzheimer’s disease (LOAD). Many of these LOAD risk-associated alleles alter disease pathogenesis by influencing innate immune responses and lipid metabolism of microglia (MG). Here we show that boosting the expression of angiotensin-converting enzyme (ACE), a genome-wide association study LOAD risk-associated gene product, specifically in MG, reduces amyloid-β (Aβ) plaque load, preserves vulnerable neurons and excitatory synapses, and significantly reduces learning and memory abnormalities in the 5xFAD amyloid mouse model of AD. ACE-expressing MG surround plaques more frequently and they have increased Aβ phagocytosis, endolysosomal trafficking and spleen tyrosine kinase activation downstream of the major Aβ receptors, triggering receptor expressed on myeloid cells 2 (Trem2) and C-type lectin domain family 7 member A (Clec7a). These findings establish a role for ACE in enhancing microglial immune function and they identify a potential use for ACE-expressing MG as a cell-based therapy to augment endogenous microglial responses to Aβ in AD. Gomez et al. show that boosting angiotensin-converting enzyme expression in microglia promotes phagocytic clearance of Aβ and endolysosomal trafficking, driven by spleen tyrosine kinase signaling in the 5xFAD transgenic model of Alzheimer’s disease.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 7","pages":"1280-1294"},"PeriodicalIF":19.4,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A blood-based epigenetic clock for intrinsic capacity predicts mortality and is associated with clinical, immunological and lifestyle factors 以血液为基础的内在能力表观遗传时钟预测死亡率，并与临床、免疫和生活方式因素有关。

IF 19.4

Nature aging Pub Date : 2025-06-04 DOI: 10.1038/s43587-025-00883-5

Matías Fuentealba, Laure Rouch, Sophie Guyonnet, Jean-Marc Lemaitre, Philipe de Souto Barreto, Bruno Vellas, Sandrine Andrieu, David Furman

{"title":"A blood-based epigenetic clock for intrinsic capacity predicts mortality and is associated with clinical, immunological and lifestyle factors","authors":"Matías Fuentealba, Laure Rouch, Sophie Guyonnet, Jean-Marc Lemaitre, Philipe de Souto Barreto, Bruno Vellas, Sandrine Andrieu, David Furman","doi":"10.1038/s43587-025-00883-5","DOIUrl":"10.1038/s43587-025-00883-5","url":null,"abstract":"Age-related decline in intrinsic capacity (IC), defined as the sum of an individual’s physical and mental capacities, is a cornerstone for promoting healthy aging by prioritizing maintenance of function over disease treatment. However, assessing IC is resource-intensive, and the molecular and cellular bases of its decline are poorly understood. Here we used the INSPIRE-T cohort (1,014 individuals aged 20–102 years) to construct the IC clock, a DNA methylation-based predictor of IC, trained on the clinical evaluation of cognition, locomotion, psychological well-being, sensory abilities and vitality. In the Framingham Heart Study, DNA methylation IC outperforms first-generation and second-generation epigenetic clocks in predicting all-cause mortality, and it is strongly associated with changes in molecular and cellular immune and inflammatory biomarkers, functional and clinical endpoints, health risk factors and lifestyle choices. These findings establish the IC clock as a validated tool bridging molecular readouts of aging and clinical assessments of IC. Fuentealba and colleagues build and validate a DNA methylation clock of intrinsic capacity (IC) to bridge resource-intensive clinical assessments of IC with molecular readouts of aging, highlighting strong links to inflammation, clinical health markers and lifestyle factors.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 7","pages":"1207-1216"},"PeriodicalIF":19.4,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Developing a blood-based epigenetic clock for intrinsic capacity 为内在能力开发一种基于血液的表观遗传时钟。

IF 19.4

Nature aging Pub Date : 2025-06-04 DOI: 10.1038/s43587-025-00899-x

Xueqing Jia, Zuyun Liu

引用次数: 0

hUSI is a robust transcriptome-based cellular senescence prediction tool hUSI是一个强大的基于转录组的细胞衰老预测工具。

IF 19.4

Nature aging Pub Date : 2025-06-03 DOI: 10.1038/s43587-025-00894-2

引用次数: 0

The secretome of senescent monocytes predicts age-related clinical outcomes in humans 衰老单核细胞分泌组预测人类年龄相关的临床结果。

IF 19.4

Nature aging Pub Date : 2025-06-03 DOI: 10.1038/s43587-025-00877-3

Bradley Olinger, Reema Banarjee, Amit Dey, Dimitrios Tsitsipatis, Toshiko Tanaka, Anjana Ram, Thedoe Nyunt, Gulzar N. Daya, Zhongsheng Peng, Mansi Shrivastava, Linna Cui, Julian Candia, Eleanor M. Simonsick, Myriam Gorospe, Keenan A. Walker, Luigi Ferrucci, Nathan Basisty

{"title":"The secretome of senescent monocytes predicts age-related clinical outcomes in humans","authors":"Bradley Olinger, Reema Banarjee, Amit Dey, Dimitrios Tsitsipatis, Toshiko Tanaka, Anjana Ram, Thedoe Nyunt, Gulzar N. Daya, Zhongsheng Peng, Mansi Shrivastava, Linna Cui, Julian Candia, Eleanor M. Simonsick, Myriam Gorospe, Keenan A. Walker, Luigi Ferrucci, Nathan Basisty","doi":"10.1038/s43587-025-00877-3","DOIUrl":"10.1038/s43587-025-00877-3","url":null,"abstract":"Cellular senescence increases with age and contributes to age-related declines and pathologies. We identified circulating biomarkers of senescence and related them to clinical traits in humans to facilitate future noninvasive assessment of individual senescence burden, and efficacy testing of novel senotherapeutics. Using a nanoparticle-based proteomic workflow, we profiled the senescence-associated secretory phenotype (SASP) in THP-1 monocytes and examined these proteins in 1,060 plasma samples from the Baltimore Longitudinal Study of Aging. Machine-learning models trained on THP-1 monocyte SASP associated SASP signatures with several age-related phenotypes in a test cohort, including body fat composition, blood lipids, inflammatory markers and mobility-related traits, among others. Notably, a subset of SASP-based predictions, including a high-impact SASP panel, were validated in InCHIANTI, an independent aging cohort. These results demonstrate the clinical relevance of the circulating SASP and identify potential senescence biomarkers that could inform future clinical studies. Olinger, Banarjee et al. use several proteomic approaches to profile the senescent monocyte secretome and identify senescence-associated circulating proteins that associate with age- and obesity-related phenotypes in two independent aging studies.","PeriodicalId":94150,"journal":{"name":"Nature aging","volume":"5 7","pages":"1266-1279"},"PeriodicalIF":19.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Editing epigenetic age 编辑表观遗传年龄。

IF 19.4

Nature aging Pub Date : 2025-06-02 DOI: 10.1038/s43587-025-00893-3

Bastiaan T. Heijmans

引用次数: 0

Pace of aging matters for healthspan and lifespan in older adults 衰老的速度关系到老年人的健康、寿命和寿命。

IF 19.4

Nature aging Pub Date : 2025-05-30 DOI: 10.1038/s43587-025-00903-4

引用次数: 0